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  • Title: Anastrozole vs Letrozole to Augment Height in Pubertal Males With Idiopathic Short Stature: A 3-Year Randomized Trial.
    Author: Zegarra W, Ranadive S, Toulan D, Neely EK.
    Journal: J Endocr Soc; 2024 Aug 27; 8(10):bvae141. PubMed ID: 39262574.
    Abstract:
    CONTEXT: Insufficient efficacy and safety data for off-label use of aromatase inhibitors to augment height in boys with short stature. OBJECTIVE: To compare anastrozole and letrozole in treatment of idiopathic short stature in pubertal boys. DESIGN: Open-label trial with 2 treatment arms. SETTING: Pediatric Endocrine Clinic at Stanford. PARTICIPANTS: A total of 79 pubertal males ≥10 years with bone age (BA) ≤ 14 years, predicted adult height (PAH) < 5th percentile or >10 cm below mid-parental height. INTERVENTION: Anastrozole 1.0 mg or letrozole 2.5 mg daily for up to 3 years. MAIN OUTCOME MEASURES: Annual hormone levels and growth parameters during treatment and a year posttherapy; annual BA and PAH (primary outcome measure); spine x-rays and dual energy X-ray absorptiometry at baseline and 2 years. RESULTS: Compared with anastrozole (n = 35), letrozole (n = 30) resulted in higher testosterone levels, lower estradiol and IGF-1 levels, and slower growth velocity and BA advance. The PAH increase observed at year 1 in both groups did not persist at years 2 and 3. Change in PAH from baseline was not different between treatment groups. In groups combined, PAH gain over 3 years vs baseline was +1.3 cm (P = .043) in linear mixed models. CONCLUSION: Letrozole caused greater deviations than anastrozole in hormone levels, growth velocity, and BA advancement, but no group differences in PAH or side effects were found. Change in PAH after 2 to 3 years of treatment was minimal. The efficacy of AI as monotherapy for height augmentation in pubertal boys with idiopathic short stature may be limited, and safety remains an issue.
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